Mitogen-activated protein kinase (MAPK) pathways mediate a variety of signals that regulate cell growth and differentiation as well as stress-induced responses in organisms ranging from yeast to mammals (Lewis et al., Adv Cancer Res, 74:49-139, 1998). The pathways consist of a cascade of kinases, a serine/threonine kinase, MAPKKK, that phosphorylates and activates a dual specificity kinase, MAPKK that in turn is capable of transferring phosphates on to threonines and tyrosines of a third enzyme, MAPK. MAPK subsequently phosphorylates and activates transcription factors, among other substrates. In mammals, the prototype MAP kinase cascade is initiated by Ras (Howe et al., Cell, 71:335-342, 1992.) and includes Raf, MEK and ERK (Lewis et al., Adv Cancer Res, 74:49-139, 1998). In Saccharomyces cerevisiae, the best characterized MAP kinase cascade is the one responding to mating pheromones. In this system, Ste11 is the MAPKKK that activates Ste7, the MEK counterpart, which in turn activates two functionally redundant MAPKs, Fus3 (Elion et al., Cell, 60:649-664, 1990) and KSS 1 (Courchesne et al., Cell, 58:1107-1119, 1989). We and others (Freed et al., Science, 265:1713-1716, 1994; Irie et al., Adv Cancer Res., 265:1716-1719, 1994) have previously shown that loss of Ste11 by gene knock out in this system, can be functionally complemented by an active mammalian Raf protein and its substrate MEK. This hybrid MAP kinase pathway is uncoupled from mating pheromone stimulation and responds to Raf or MEK activators with expression of the HIS3 gene that allows growth on media lacking histidine.